This is a multidisciplinary research project on the pathogenesis and prevention of mineralocorticoid-induced hypertension in experimental animals. We now have methodology which allows us to profile the various key enzymes in adrenal steroid hormone biosynthesis; cholesterol side chain cleavage, ll Beta-hydroxylase, l8-hydroxylase and 2l-hydroxylase. In addition, we can profile the various corticosteroids in peripheral plasma; aldosterone, corticosterone l8-hydroxy-DOC, and DOC. Using these in vitro and in vivo assays we are engaged in studies of the SHR rat as well as other forms of experimental hypertension. We hope to establish if there is a relationship between adrenal cortical dysfunction and the pathogenesis of spontaneous hypertension. In this study the functional studies of the adrenal cortex are combined with studies of adrenal cortex ultrastructure. In models of experimental hypertension in which there is some evidence of mineralocorticoid involvement, we are investigating the possibility of prevention of hypertensive cardiovascular disease by active immunization with BSA conjugates of these mineralocorticoids. Finally, we are examining the effect of stress on the competition for NADPH for steroid hydroxylation reactions in adrenal mitochondria and will try to determine the role of such competition in the pathogenesis of stress-related hypertensive cardiovascular disease. BIBLIOGRAPHIC REFERENCES: Molteni, A., P.A. Nickerson, S. Gallant, A.C. Brownie. Resistance of W/Fu Rats to adrenal Regeneration Hypertension. Proc. Soc. Exp. Biol. and Med. l50:80-84, 1975. Bergon, L., A.C. Brownie. Adrenal Mitochondrial and Serum Corticosteroid Studies in Rats Resistant to Adrenal-Regeneration Hypertension (ARH). Endocrinology, l976. in press.